Abstract
Treatment outcomes for chronic myelogenous leukemia (CML) have shown major improvements as a result of the development of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been rarely achieved. CML cells are protected from cytotoxic insults, including those by TKIs, through various collaborative BCR-ABL1- mediated and -independent mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These protective mechanisms include overlapping cell signaling pathways for normal hematopoietic proliferation, modulation of molecules associated with the BCL2 family protein-regulated programmed cell death pathway, autophagic cell protection capability, bone marrow environment-mediated cell protective signaling, abnormally upregulated genetic instability and other BCRABL1- independent kinase activities. To develop a more effective treatment strategy for a cure by means of total leukemic cell killing, a thorough understanding of how CML cells survive and resist cytotoxic insults is essential. In this article, we review current knowledge about multifaceted BCR-ABL1-related and -unrelated mechanisms for survival and death of CML cells and present suggestions for the development of new therapeutic strategies for complete elimination of residual CML cells during TKI treatment.
Keywords: Apoptosis, autophagy, CML, gene instability, microenvironment, stem cell
Current Cancer Drug Targets
Title:Multifaceted Mechanisms for Cell Survival and Drug Targeting in Chronic Myelogenous Leukemia
Volume: 13 Issue: 1
Author(s): J. Kuroda, Y. Shimura, M. Yamamoto-Sugitani, N. Sasaki and M. Taniwaki
Affiliation:
Keywords: Apoptosis, autophagy, CML, gene instability, microenvironment, stem cell
Abstract: Treatment outcomes for chronic myelogenous leukemia (CML) have shown major improvements as a result of the development of the tyrosine kinase inhibitors (TKIs) imatinib, nilotinib and dasatinib for the disease-specific molecular target BCR-ABL1 tyrosine kinase (TK), but a cure of CML by BCR-ABL1 TKIs has been rarely achieved. CML cells are protected from cytotoxic insults, including those by TKIs, through various collaborative BCR-ABL1- mediated and -independent mechanisms, as well as cell-intrinsic and -extrinsic molecular mechanisms. These protective mechanisms include overlapping cell signaling pathways for normal hematopoietic proliferation, modulation of molecules associated with the BCL2 family protein-regulated programmed cell death pathway, autophagic cell protection capability, bone marrow environment-mediated cell protective signaling, abnormally upregulated genetic instability and other BCRABL1- independent kinase activities. To develop a more effective treatment strategy for a cure by means of total leukemic cell killing, a thorough understanding of how CML cells survive and resist cytotoxic insults is essential. In this article, we review current knowledge about multifaceted BCR-ABL1-related and -unrelated mechanisms for survival and death of CML cells and present suggestions for the development of new therapeutic strategies for complete elimination of residual CML cells during TKI treatment.
Export Options
About this article
Cite this article as:
Kuroda J., Shimura Y., Yamamoto-Sugitani M., Sasaki N. and Taniwaki M., Multifaceted Mechanisms for Cell Survival and Drug Targeting in Chronic Myelogenous Leukemia, Current Cancer Drug Targets 2013; 13 (1) . https://dx.doi.org/10.2174/1568009611309010069
DOI https://dx.doi.org/10.2174/1568009611309010069 |
Print ISSN 1568-0096 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5576 |
Call for Papers in Thematic Issues
Advances in Cancer Biomarkers and Potential Drug Targets: From Diagnosis to Therapy
Cancer biomarkers play a crucial role in the diagnosis, prognosis, and treatment of cancer. They provide valuable information for cancer detection, risk assessment, treatment selection, and monitoring response to therapy. With advancements in molecular biology and high-throughput technologies, there has been an increasing interest in identifying and characterizing cancer biomarkers ...read more
Novel Therapeutic Approaches to Target Drug Resistant Tumors
With the development of disciplines such as chemical biology and molecular biology, the genes or proteins closely related to tumor occurrence and development have gradually become clear. Targeted therapies targeting these genes or proteins provide more effective methods for tumor treatment. Tumor targeted drugs generally only act on specific targets ...read more
ROLE OF IMMUNE AND GENOTOXIC RESPONSE BIOMARKERS IN TUMOR MICROENVIRONMENT IN CANCER DIAGNOSIS AND TREATMENT
Biological biomarkers have been used in medical research as an indicator of a normal or abnormal process inside the body, or of a disease. Nowadays, various researchers are in process to explore and investigate the biological markers for the early assessment of cancer. DNA Damage response (DDR) pathways and immune ...read more
Targeting the battlefield between host and tumor: basic research and clinical practice on reshaping tumor immune microenvironment
Immune system protects host against malignant tumors through effector cells and molecules. Cancer development and its response to therapy are regulated by inflammation, which either promotes or suppresses cancer progression. Chronic inflammation facilitates cancer progression and treatment resistance, whereas induction of acute inflammatory reactions often lead to anti-cancer immune responses. ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Attenuated Oncolytic Measles Virus Strains as Cancer Therapeutics
Current Pharmaceutical Biotechnology Withdrawal Notice: Role, Significance and Association of microRNA-10a/b in Physiology of Cancer
MicroRNA Analysis of Fish IL-1β and Derived Peptide Sequences Indicates Conserved Structures with Species-Specific IL-1 Receptor Binding: Implications for Pharmacological Design
Current Pharmaceutical Design Recent Developments on 1,2,4-Triazole Nucleus in Anticancer Compounds: A Review
Anti-Cancer Agents in Medicinal Chemistry Common Pathways in Health Benefit Properties of RSV in Cardiovascular Diseases, Cancers and Degenerative Pathologies
Current Pharmaceutical Biotechnology Genetic Idiotypic and Tumor Cell-Based Vaccine Strategies for Indolent Non Hodgkins Lymphoma
Current Gene Therapy The Human L1 Element: A Potential Biomarker in Cancer Prognosis, Current Status and Future Directions
Current Molecular Medicine Phosphatidylinositol 3-Kinase Isoforms as Novel Drug Targets
Current Drug Targets Atomic Force Microscopy: The Characterisation of Amyloid Protein Structure in Pathology
Current Topics in Medicinal Chemistry Dissecting Bortezomib: Development, Application, Adverse Effects and Future Direction
Current Pharmaceutical Design Targeting EZH2 for Cancer Therapy: Progress and Perspective
Current Protein & Peptide Science The Impact of Thrombopoietin on Clinical Practice
Current Pharmaceutical Design Lumiflavin Enhances the Effects of Ionising Radiation on Ovarian Cancer Stem-Like Cells by Inhibiting Autophagy
Anti-Cancer Agents in Medicinal Chemistry IAPs as a Target for Anticancer Therapy
Current Cancer Drug Targets “Endothelial Progenitor Cells” as a Therapeutic Strategy in Cardiovascular Disease
Current Vascular Pharmacology Molecular Biomarkers for Lung Adenocarcinoma: A Short Review
Current Cancer Therapy Reviews On the Origin of Epidermal Cancers
Current Molecular Medicine IMGT Colliers de Perles: Standardized Sequence-Structure Representations of the IgSF and MhcSF Superfamily Domains
Current Bioinformatics Revisiting the ABCs of Multidrug Resistance in Cancer Chemotherapy
Current Pharmaceutical Biotechnology Unravelling the Role of Infectious Agents in the Pathogenesis of Human Autoimmunity: The Hypothesis of the Retroviral Involvement Revisited
Current Molecular Medicine